We have discovered a paradoxical increase in immunoreactive glucagon (IRG) secretion and a diminished insulin response to intravenous glucose in ventromedial hypothalamic (VMH) lesioned weanling rats. Preliminary experiments with isolated perifused pancreatic islets from VMH lesioned rats also revealed a paradoxical increase in glucagon and a diminished insulin secretion in response to a change in glucose from 100 to 300 micrograms percent. This proposal outlines the steps necessary to determine: 1) if the abnormal glucose-sensing function of the A-cell in VMH lesioned rats is comparable to the abnormal A-cell function of human diabetes mellitus particularly that found in obese hyperinsulinemic adult-type diabetes and its murine counterpart the genetically obese hyperglycemic mouse, ob/ob; 2) if the abnormal A-cell function is related to changes in pancreatic islet D-cell somatostatin and/or insulin content or secretion; and 3) if gastric D-cells and somatostatin release are under the same regulatory influence as are pancreatic D-cells.